Structural basis of phosphatidylcholine recognition by the C2-domain of cytosolic phospholipase A(2)α Journal Article
| Authors: | Hirano, Y.; Gao, Y. G.; Stephenson, D. J.; Vu, N. T.; Malinina, L.; Simanshu, D. K.; Chalfant, C. E.; Patel, D. J.; Brown, R. E. |
| Article Title: | Structural basis of phosphatidylcholine recognition by the C2-domain of cytosolic phospholipase A(2)α |
| Abstract: | Ca2+-stimulated translocation of cytosolic phospholipase A2α (cPLA2α) to the Golgi induces arachidonic acid production, the rate-limiting step in pro-inflammatory eicosanoid synthesis. Structural insights into the cPLA2α preference for phosphatidylcholine (PC)-enriched membranes have remained elusive. Here, we report the structure of the cPLA2α C2-domain (at 2.2 Å resolution), which contains bound 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) and Ca2+ ions. Two Ca2+ are complexed at previously reported locations in the lipid-free C2-domain. One of these Ca2+ions, along with a third Ca2+, bridges the C2-domain to the DHPC phosphate group, which also interacts with Asn65. Tyr96 plays a key role in lipid headgroup recognition via cation-π interaction with the PC trimethylammonium group. Mutagenesis analyses confirm that Tyr96 and Asn65 function in PC binding selectivity by the C2-domain and in the regulation of cPLA2α activity. The DHPC-binding mode of the cPLA2α C2-domain, which differs from phosphatidylserine or phosphatidylinositol 4,5-bisphosphate binding by other C2-domains, expands and deepens knowledge of the lipid-binding mechanisms mediated by C2-domains. © 2019, Hirano et al. |
| Keywords: | molecular biophysics; chicken; structural biology; human; c2-domain of cytoplasmic phospholipase a2 alpha; structural mapping of phosphatidylcholine binding site; structure-function analyses |
| Journal Title: | eLife |
| Volume: | 8 |
| ISSN: | 2050-084X |
| Publisher: | eLife Sciences Publications Ltd. |
| Date Published: | 2019-05-03 |
| Start Page: | e44760 |
| Language: | English |
| DOI: | 10.7554/eLife.44760 |
| PUBMED: | 31050338 |
| PROVIDER: | scopus |
| PMCID: | PMC6550875 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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